The translational product of the v-sis oncogene is a disulfide- linked homodimer which is closely related to platelet-derived growth factor (PDFG). Deletion mutagenesis of the v-sis gene was used to identify an internal region of 89 codons comprising the minimal transforming domain. Oligonucleotide-directed mutagenesis within the minimal transforming domain was used to individually change each of the eight cysteine codons to serine codons. Analysis of these mutants revealed that all cysteine residues were necessary for disulfide-linked dimer formation. In contrast, only four of the cysteine residues were found to be essential for transforming activity. Deletion mutagenesis within the minimal transforming domain was used to map structurally important regions. Characterization of the proteins encoded by these mutants resulted in the identification of inactive homodimers. The v-sis gene has been overexpressed using the baculovirus vector system. The v-sis protein expressed in this system efficiently dimerizes and has high specific activity when tested for mitogenesis on NIH/3T3 cells. Therefore, this system will be used to express and further characterize mutant v-sis proteins.